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While with Kira, Odo is massaging her for a springball injury. During, he says he's leaving soon, having received a message from GulRussol, who used to be one of his most reliable informants. Russol was executed when Cardassia joined the Dominion, or so Odo thought. Even though he is skeptical, he owes it to Russol to find out. He sets out for a barren moon on the USS Rio Grande.

Meanwhile, Miles O'Brien is in dire straits. CaptainSisko has ordered him to get the USS Defiant's gravity net up and running in three days, even though the station already needs far too many repairs... and the needed graviton stabilizer won't be available for three weeks. After he leaves, Nog offers the chief his help, saying O'Brien needs to form a relationship with the quartermaster who has the stabilizer in order to be on the top of his list. O'Brien thinks that Nog will only get him in deeper trouble, and tells him he can go ahead and try as long as he doesn't get them court martialed.

On the barren moon, Weyoun's offer to trade valuable intelligence about the Dominion in exchange for asylum in the Federation seems too good an offer to pass up. Weyoun insists they hurry as he's being searched for, but Odo waits, forcing him to explain himself. He says he's under pressure because the Dominion War was supposed to be over and he'll take the blame. Furthermore, he confirms a rumor Odo tells him about a Ketracel-white facility in Sector 507. Odo then agrees to take Weyoun back to Deep Space 9.

After speaking with the quartermaster, Chief Willoughby, Nog learns he won't get a stabilizer for another week, but the USS Sentinel has one now. Nog just needs to know what they need. Nog talks O'Brien into giving him his authorization code for the sake of expediency, and the Ferengi begins wheeling and dealing for the stabilizer in the chief's name.

Odo and Weyoun don't get very far when they receive a transmission from Cardassia. Odo is surprised to see that the transmission is from LegateDamar – and Weyoun.

It turns out that the Weyoun with Odo is clone number six (the Weyoun the crew has had the majority of previous dealing was the fifth clone who died after a transporter "accident"), who is apparently defective as he has a lack of faith in the Founders. The Weyoun clone 7, the one with Damar, orders clone 6 to activate his termination implant, a device all Vorta clones have inside their brains. When 6 refuses, Damar vows that the runabout will never return to DS9. After the transmission ended, Weyoun 6 admits to Odo the real reason he's defecting is that he felt the war was wrong. Odo is surprised when he hears this, and tells him his opinion makes perfect sense.

On Cardassia, Damar tells Weyoun 7 they will have to order the Jem'Hadar to destroy the runabout; however, Weyoun refuses to harm a Founder. Damar is able to prod him into agreeing, as Odo does not consider himself a Founder and they will not need to tell the Jem'Hadar, or anyone else.

On DS9, O'Brien learns from an angry Kira that the captain's desk is missing. O'Brien catches up with Nog at the Replimat and gets the full story. Nog explains that it is on loan to Al Lorenzo, chief of operations on Decos Prime, who wants a holophoto of himself sitting behind it (he collects such photos). Nog has set up a chain of deals: in exchange for the loan of the desk, Lorenzo will give O'Brien an induction modulator, which O'Brien can then trade to the USS Musashi for a phaser emitter. The phaser emitter will then go to the Sentinel which has the graviton stabilizer that O'Brien (and the Defiant) needs. As O'Brien panics, seeing disaster ahead, Nog tells the chief to have faith in the Great Material Continuum, which Ferengi believe flows through the universe like a river, bringing people the things they need from those that have, and back again.

Meanwhile, on the Rio Grande, Weyoun describes a nightmare, a product of his betrayal. Odo sympathizes, but then a Jem'Hadarfighter appears and tries to shoot down and destroy the runabout.

Weyoun 6 can't believe they're firing on the ship with Odo on board. He gives details to Odo about the weakness of the fighter which allows Odo to destroy it with a sustained twin-Phaser blast. Weyoun is distraught, having now caused the death of loyal Dominion subjects. Odo attempts to probe him, saying his belief in the Founders was built into his genetic code, but he replies that is what gods do.

Meanwhile, O'Brien becomes increasingly anxious when Nog disappears from the station (having used the access code to get access to a runabout). Things get worse when General Martok finds his 16 cases of bloodwine missing. Worf promises to find it.

At Dominion Headquarters, Damar and Weyoun 7 are astonished that a simple runabout could destroy a Jem'Hadar fighter, and resolve to simply send more ships from a nearby base in the Olmerak system. At that moment, the Female Changeling arrives and inquires what they are sending ships after. They only say that they found a runabout spying on the base and are sending ships to destroy it. However, Damar notices something odd about the Founder: her face is parched with very noticeable wrinkles. She quickly morphs the wrinkles away, insists she is alright, and orders the temperature lowered.

As they continue their journey back to the station, Weyoun 6 tells Odo the story of how the Vorta came to be in the service of the Founders. After Odo expresses satisfaction that his people are capable of kindness, and Weyoun suggests Odo cares for his people in spite of their war, Weyoun relates a startling revelation: the Founders are dying.

The entire Great Link is suffering from a strange disease (a morphogenic virus), which Weyoun witnessed from the female changeling. Only Odo, it seems, is not infected. Weyoun suggests it could be an opportunity for Odo to take over the Dominion and stop the war, but then more Jem'Hadar ships show up, so Odo takes the runabout into an ice field and hides it in a large chunk of ice and powers it down.

Back on the station, O'Brien plans to make a new desk for Sisko, and asks Bashir for help. He has a plain white desk he plans to paint, but Bashir is sarcastically skeptical. Kira comes in not believing what she's seeing, and, soon, Martok comes in and angrily points O'Brien out. He takes O'Brien down to the cargo bay and shows him his authorization code, demanding that the bloodwine be returned in 24 hours. Things are heating up for O'Brien.

Within hours, the Jem'Hadar flush them out, and Odo makes a run for it.

Knowing that the situation is hopeless, and to save Odo's life so that at least one Founder survives, Weyoun 6 contacts Weyoun 7 and asks him to call off the attack. Weyoun 7 watches as Weyoun 6 activates his termination device. Satisfied, Weyoun 7 orders the Jem'Hadar ships to stop attacking. Meanwhile, Weyoun 6 asks Odo for his blessing before he dies. Although Odo despises the idea that the Vorta see the Founders as gods, he grants Weyoun 6 his wish.

Back on DS9, the Great Material Continuum comes through. Nog has returned along with Sisko's desk, looking spiffier than ever, the stabilizer is on hand, and the captain is happy. Even Martok is happy; in place of the bloodwine his wife sent him are 16 cases of 2309 bloodwine: a superior vintage. O'Brien decides to plunge right into the river to get some Saurian Brandy for Captain Sisko.

Meanwhile, in his quarters, Odo reflects over the blessing he gave Weyoun and how content the Vorta looked when he died. Kira tells him that Weyoun was lucky, as he died with one of his gods smiling at him. The two then discuss the Founders' disease, and Kira notes that they will get more dangerous if they're desperate to survive. Odo remarks that regardless of who wins the war, it feels like he will lose either way.

"You have to have faith, Chief."
"In a rumor?!"
"No... in the Great Material Continuum!"
(sighs) "Who are they?!"
"It's not a 'they', it's the force that binds the universe together."
"Oh, I must have missed that class at Engineering School."

- Nog And O'Brien

"Has it ever occurred to you that you believe the Founders are gods because that's what they want you to believe? That they built that into your genetic code?"
"Of course they did. That's what gods do. After all, why be a god if there's no one to worship you?"

- Odo and Weyoun 6

"Where are my cases of bloodwine?!"
"I do not know, General, but I promise you I will find out."

- Martok and Worf

"We spotted a Federation runabout spying on our base in the Olmerak system."
"Surely one ship shouldn't be much of a threat."
"We'll have it destroyed within the hour."

- Damar, Female Changeling and Weyoun 7

"Then let's just say I left Cardassia because my life was in danger."
"From whom?"
"Everyone."
"Aren't you being a little paranoid?"
"Of course I'm paranoid, everyone's trying to kill me!"

- Weyoun 6 and Odo

"What do you think?"
"It's white."
"I know it's white, I'm gonna paint it."
"It's the wrong shape. The wrong height. The wrong width. Other than that it's perfect. The captain will never suspect you switched desks on him."
"Julian, I need help, not sarcasm."
"I'm afraid Nog is the only one that can help you now."
"If he gets back to the station before the captain does."
"Maybe he's not coming back. Maybe he's decided to make a run for it."
(Kira enters) "That isn't the captain's desk!"
"He's gonna paint it."
"Get it out of here!"

- O'Brien and Bashir with a small interruption from Kira, about the captain's desk that Nog loaned out

"It's just such an honor to be with a g... (clears throat) a security officer."

- Weyoun 6

"All right, you can start by telling me how one runabout is going to survive an assault by four Jem'Hadar ships."
"I'm sure you'll think of something."

- Odo and Weyoun 6

"This isn't easy for you, but you have to remember, they started this war. You didn't."
"That's true. But I know now, whichever side wins, one thing is certain: I'm going to lose."

- Kira and Odo

"I dont know how you did it, Nog."
"I never lost faith in the Great Material Continuum. "
"Ah, like you say, the river will provide."
"Chief!"
"The waters just got choppy again..."

Philip Kim's original idea for this episode involved Weyoun coming to Sisko to ask for his help because the Founders are breeding a new race called the Modain, who are to replace the Jem'Hadar. The Modain are far tougher and more aggressive than the Jem'Hadar, and even more loyal to the Founders. Weyoun convinces Sisko that it would be in everybody's best interest to destroy the breeding facility where the Modain are being developed. After destroying the facility however, Sisko discovers that Weyoun was lying – the Modain were not being bred to replace the Jem'Hadar, they were being bred to replace the Vorta. Ira Steven Behr had been looking for a good Weyoun/Odo story since the sixth season, and he believed that Kim's idea could be modified to fit. Consequently he assigned the script to David Weddle and Bradley Thompson, who altered Kim's story into the final episode. (Star Trek: Deep Space Nine Companion)

The origins (or possible origins) of the Vorta are revealed in this episode. Ira Steven Behr came up with this story, and of it, he says, "I like to get the audience thinking one way about a character or a race, making them think that these are definitely the bad guys. Then you slip something like this in so they have to reevaluate the opinion you've already given them. These are still the bad guys, but now, at least, you understand something about why. So I just loved that the Vorta, this calculating, Machiavellian race, started out as Hobbit-like cute little creatures who were genetically altered and directed to do these horrible things." (Star Trek: Deep Space Nine Companion)

The writers saw Odo's reluctant acceptance that for the Vorta, he truly is a god, as being his first step in deciding to return to the Founders at the end of the series. (Star Trek: Deep Space Nine Companion)

Of the B-story, which is based on the 1961Joseph Heller novel Catch 22, with Nog taking the role of Milo Minderbinder, Aron Eisenberg states, "This was Nog taking the same energy and Ferengi ideals he'd had before he joined Starfleet and incorporating them into his goals in Starfleet. What I love about having an honest Ferengi in Starfleet is that he knows how to manipulate the situation. In Starfleet, you go through certain channels to get things done. It's all very official. Nog just feels that you don't have to. You can do it this way and it works just as easily and it's much faster. He thinks it's perfectly natural to do this. No one else in Starfleet would have done things this way except Nog." (Star Trek: Deep Space Nine Companion)

Jeffrey Combs has stated that this was his favorite episode, not only because of the amount of screen time he got, but also because of the opportunity of playing two completely different 'types' of Weyoun in a single episode; "One Weyoun was defective, but that didn't mean that he was weak or that he wasn't manipulative or that he couldn't see what the other Weyoun is doing. Finding the right balance was tricky, so it really was my most challenging show. I would say to myself, 'Okay, now, how would that Weyoun say that line and how would this Weyoun react to it'. I tried to make Weyoun 6 a Weyoun of a different color, a Weyoun who could align himself with the Federation and see the flaws in his leaders. This actually appealed to me. I've always thought that Weyoun had some innate goodness in him somewhere. It's just difficult finding it because the Vorta are genetically designed to be loyal. But one person's defectiveness is another person's enlightenment. He was blind but now he could see. And for that, he was labeled a 'problem.' That was fun to play. I thought of each Weyoun as a different slice of the same pizza. One just didn't have any pepperoni on it." (Star Trek: Deep Space Nine Companion)

Like a few other Deep Space Nine episodes, the final title works equally well for both the A and B stories (Rio Grande means Great River, referring to the Great Material Continuum; treachery refers to Weyoun 6's defection and to O'Brien's feelings toward Nog midway through the episode; and faith to Weyoun's loyalty to Odo and Nog's faith in the Great Material Continuum.)

The Female Changeling begins to exhibit the effects of the morphogenic virus in this episode. The virus was created by Section 31, who infected Odo with it in the fourth season episode "Homefront". Odo in turn infected the Great Link in the season 4 finale "Broken Link". Presumably, he was also "cured" of the virus in that episode when he was made a solid. He was subsequently re-infected by the Female Changeling in the sixth season episode "Behind the Lines", which explains why Odo and Weyoun believe that Odo is in fact free of the disease even though other Founders have begun to exhibit symptoms, as well as why Odo, who was initially infected long before any other Founder, was the last to exhibit symptoms.

It's possible that GulRussol is the contact to whom Odo speaks in "Improbable Cause"; he mentions that Russol was one of his most reliable contacts, and in "Improbable Cause", he obviously places great faith in his informant, so there is a possibility that they are one and the same.

This is the first episode in which Damar expresses a strong sense of patriotism, mentioning all that Cardassia has lost in the Dominion War. This would go on to be a major factor in his character turning against the Dominion in the ten-hour, nine episode arc which closes the series.

On the runabout, Weyoun was trying to eat a pepperonipizza with chopsticks.

The B-story of this episode recalls both the first season episode "Progress" and the fifth season episode "In the Cards" insofar as Nog is trying to acquire something specific, but keeps getting other items in an attempt to work his way back to what he originally wanted.

It is not clear why air and an appropriate temperature are needed to keep Odo alive; since he does not eat, he presumably has no metabolism that would need oxygen as a fuel and temperature as a catalyst. He actually seems to stand the freeze without too many problems, as opposed to Weyoun. "Chimera" also sees another changeling having no problem with at least changing into something that can live in space.

This is the second of three times after the discovery of the Dominion that Odo is referred to as a "shapeshifter" instead of a Changeling; Damar uses this term when talking to Odo. Drex used it previously in "The Way of the Warrior", and Odo himself would later use it in "Chimera".

This was the first named appearance of the Rio Grande since "The Ascent", finally confirming that the ship was salvaged and repaired.